IFNA5 - interferon alpha 5 |Elisa - Clia - Antibody - Protein

Background

Interferon-alpha 5 (IFN-α5) is part of the type I interferon family, a group of cytokines that play a critical role in the innate immune response. Type I interferons, including IFN-α5, are primarily responsible for defending the body against viral infections and stimulating immune responses. The IFN-α family includes several subtypes, all of which are encoded by distinct genes, with similar but non-identical functions. IFN-α5, like other interferons, is produced by immune cells such as dendritic cells and macrophages in response to viral infection or other pathogenic threats.

The production of IFN-α5 is induced by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), that recognize pathogen-associated molecular patterns (PAMPs). Once produced, IFN-α5 exerts its effects by binding to the interferon-alpha/beta receptor (IFNAR), initiating a cascade of intracellular signaling events that culminate in the activation of numerous interferon-stimulated genes (ISGs). These ISGs orchestrate the antiviral state, hindering viral replication and spread.

While IFN-α2 is the most widely studied and clinically utilized subtype, IFN-α5 and other subtypes have unique properties and may exhibit different antiviral, antitumor, and immunomodulatory effects. IFN-α5 has shown significance in antiviral responses and potentially in autoimmune diseases and cancer through its interaction with immune cells and modulation of immune pathways.

Protein Structure

The protein structure of IFN-α5 is characteristic of type I interferons, sharing significant homology with other IFN-α subtypes but with subtle differences that may impact its receptor binding and biological activity.

Primary Structure:

• IFN-α5 is a glycoprotein composed of approximately 165 amino acids. It is encoded by the IFNA5 gene located on chromosome 9 in humans, within a cluster of interferon-alpha genes.
• The protein is synthesized as a precursor protein with a signal peptide at the N-terminus. This signal peptide is essential for directing the nascent protein to the secretory pathway and is cleaved during maturation, resulting in the mature IFN-α5 protein.

Secondary and Tertiary Structure:

• The mature IFN-α5 protein has a helical structure, dominated by five closely packed α-helices. These helices are organized in a manner that allows for optimal receptor binding and signaling. The helical bundle structure is conserved across type I interferons and is crucial for interacting with the IFNAR1 and IFNAR2 receptor subunits.
• The tertiary structure of IFN-α5 forms a compact, globular protein. Its structure is stabilized by disulfide bonds that ensure proper folding and function. These bonds are also important for the protein's stability in the extracellular environment.

Quaternary Structure:

• Like other type I interferons, IFN-α5 functions as a monomer when secreted, but upon binding to its receptor (IFNAR), it induces dimerization of the receptor subunits, activating downstream signaling pathways.

Post-Translational Modifications:

• IFN-α5 undergoes glycosylation, a critical post-translational modification that influences the protein's stability, solubility, and biological activity. Glycosylation also affects its half-life and interaction with the immune system.

Classification and Subtypes

IFN-α5 is classified under the type I interferon family, which includes IFN-α, IFN-β, IFN-ε, IFN-κ, and IFN-ω. Within the IFN-α family, there are at least 13 different subtypes, each encoded by a separate gene but sharing similar sequences and functions.

While the IFN-α subtypes all act through the same receptor complex (IFNAR), they can have varying potency and specificity in terms of antiviral, antitumor, and immunoregulatory effects. These differences arise from minor variations in their amino acid sequences, which can influence their interaction with the receptor and downstream signaling.

Function and Biological Significance

Antiviral Activity:

• IFN-α5, like other type I interferons, plays a critical role in antiviral defense. Upon binding to the IFNAR complex, IFN-α5 activates the JAK-STAT signaling pathway, which leads to the transcription of hundreds of interferon-stimulated genes (ISGs). These ISGs encode proteins that work to inhibit viral replication, degrade viral RNA, and block viral protein synthesis.
• IFN-α5 has been shown to have potent activity against a variety of RNA viruses, including hepatitis C virus (HCV), influenza, and coronaviruses. While IFN-α2 remains the most widely used subtype in antiviral therapies, studies suggest that IFN-α5 may also play a role in enhancing the body's antiviral state.

Immunomodulation:

• IFN-α5 modulates the activity of various immune cells, including natural killer (NK) cells, T cells, and macrophages. It enhances the cytotoxic activity of NK cells, promoting the destruction of virus-infected cells and tumor cells. Additionally, it induces antigen presentation by upregulating MHC class I molecules, which helps T cells recognize and eliminate infected or abnormal cells.
• IFN-α5 also influences the balance of T-helper cell responses, promoting a Th1 response that is critical for controlling intracellular pathogens and tumors.

Antiproliferative and Antitumor Effects:

• In addition to its antiviral properties, IFN-α5 has antiproliferative effects, meaning it can inhibit the growth and division of cells. This property is particularly relevant in the context of cancer therapy, where IFN-α5 can slow down the growth of tumor cells by inducing cell cycle arrest and promoting apoptosis (programmed cell death).
• Furthermore, IFN-α5 can enhance the immune system's ability to detect and eliminate cancerous cells, making it a potential candidate for immunotherapy. While IFN-α2 has been the most widely used in cancer treatment, research is exploring the potential of other subtypes, including IFN-α5.

Regulation of Inflammation:

• IFN-α5 plays a role in regulating inflammatory responses, primarily by modulating the production of pro-inflammatory cytokines and chemokines. In cases of viral infection, this helps to recruit immune cells to the site of infection and initiate the immune response. However, excessive production of IFN-α5 can contribute to chronic inflammation and may play a role in autoimmune diseases.

Clinical Issues

Despite its strong antiviral and immunomodulatory properties, IFN-α5 is less commonly used in clinical settings compared to IFN-α2. However, it has potential therapeutic implications for viral infections, cancer, and autoimmune diseases.

Viral Infections:

• Like other type I interferons, IFN-α5 could be considered for the treatment of chronic viral infections, such as hepatitis B and hepatitis C. However, its clinical application is limited, and IFN-α2 is more widely used in these contexts due to better-studied efficacy and safety profiles.

Cancer Therapy:

• IFN-α5, with its antiproliferative and pro-apoptotic properties, has potential as a cancer therapy. It could be used in the treatment of cancers such as melanoma, renal cell carcinoma, and leukemia. However, more research is needed to fully understand its potential in comparison to other interferon subtypes.

Autoimmune Diseases:

• Overproduction of IFN-α5 and other type I interferons has been implicated in the pathogenesis of autoimmune diseases, particularly systemic lupus erythematosus (SLE). Elevated levels of type I interferons in SLE patients contribute to immune system hyperactivation, production of autoantibodies, and chronic inflammation.

Side Effects:

• Like other interferons, IFN-α5 is associated with a range of side effects when used therapeutically, including flu-like symptoms (fever, fatigue, muscle aches), neuropsychiatric effects (depression, anxiety), and myelosuppression (bone marrow suppression). These side effects have limited the long-term use of interferons in clinical practice.

Summary

Interferon-alpha 5 (IFN-α5) is a member of the type I interferon family, playing a critical role in antiviral defense, immune modulation, and tumor suppression. Structurally, IFN-α5 shares significant similarities with other type I interferons, consisting of α-helices that enable its interaction with the IFNAR receptor, leading to the activation of the JAK-STAT signaling pathway and transcription of interferon-stimulated genes. While it shares common functions with other IFN-α subtypes, IFN-α5 exhibits unique antiviral and immunomodulatory properties, making it an important, though less studied, component of the immune system. Its therapeutic potential in viral infections, cancer, and autoimmune diseases is promising, but its clinical use is limited due to side effects and the availability of better-studied interferon subtypes.